Insight on nano drug delivery systems with targeted therapy in treatment of oral cancer.

Oral cancer is a type of cancer that develops in the mouth and is one of the deadliest malignancies in the world. Currently surgical, radiation therapy, and chemotherapy are most common treatments. Better treatment and early detection strategies are required. Chemotherapeutic drugs fail frequently due to toxicity and poor tumor targeting. There are high chances of failure of chemotherapeutic drugs due to toxicity. Active, passive, and immunity-targeting techniques are devised for tumor-specific activity. Nanotechnology-based drug delivery systems are the best available solution and important for precise targeting. Nanoparticles, liposomes, exosomes, and cyclodextrins are nano-based carriers for drug delivery. Nanotechnology is being used to develop new techniques such as intratumoral injections, microbubble mediated ultrasonic therapy, phototherapies, and site-specific delivery. This systematic review delves into the details of such targeted and nano-based drug delivery systems in order to improve patient health and survival rates in oral cancer.

Fabrication, optimization, and in vitro evaluation of docetaxel-loaded nanostructured lipid carriers for improved anticancer activity.

Lung cancer is the leading cause of cancer-related deaths in both men and women worldwide. It is the leading cancer killer in both men and women in every Ethnic Group. A major problem associated with chemotherapies against their lung cancer is the lack of selective toxicity, which results in a narrow therapeutic index thereby compromising clinical prognosis. To circumvent these challenges, the present investigation sought to develop a docetaxel-loaded nanostructured lipid carrier system (DTX-NLCS) for the treatment of lung cancer. A 3-factor/3-level Box-Behnken Design was applied to systematically optimize the DTX-NLCS parameters. The amount of drug, emulsifier concentration, and homogenization speed was selected as independent variables, while the particle size and % entrapment efficiency (%EE) were selected as dependent variables. The optimized batch parameters were 29.81 mg drug, 19.97% w/w emulsifier, and 13 200 (rpm) speed of homogenization with a mean particle size of 154.1 ± 3.13 nm and a mean %EE of 86.12 ± 3.48%. The in vitro lipolysis experiments revealed that the optimized DTX-NLCs were stabilized by 10% w/w PEG 4000 mono-stearate and exhibited an anti-lipolytic effect. Furthermore, the in vitro gastrointestinal stability studies (at pH-1.2, pH-4.5, pH-6.8, and pH-7.4) revealed that the optimized developed system could withstand various GI tract media. The in vitro dissolution studies depicted a pH-independent controlled-release consistent with the Weibull model. In vitro cytotoxicity studies using NCI-H460 cell lines further revealed that there was a reduction in IC50 values in the DTX-NLCS treated cells as compared to those treated with the pure drug, indicating an improved efficiency for the developed system.

Optimization and in vivo evaluation of quetiapine-loaded transdermal drug delivery system for the treatment of schizophrenia.

The prevailing studies were carried out to formulate and optimize the quetiapine transdermal matrix patch by the usage of Box-Behnken design for ameliorated bioavailability when contrasted with conventional drug delivery. The Box-Behnken design with three-level and three-factor was utilized to explore the intermingle impact of critical attributes on tensile strength, in vitro drug release, and flux. Optimized formulation was characterized for Fourier transform infrared, differential scanning calorimetry, in vivo pharmacokinetics, and skin irritation along with stability studies. The inference of the finalized batch (F14) depicted the flux of 51.81 ± 0.32 µg/h/cm2, TS of 6.46 ± 0.56 MPa, and the % drug release after 20 h of 82.98 ± 1.48% with no remarkable variation even after 6 months stability studies. Correlation between predicted and the observed values of the dependent variables was very closer. Optimized quetiapine transdermal patch did not exert any symptoms of skin irritation. The bioavailability of quetiapine was enhanced almost 4.59 times after topical delivery when contrasted with the conventional dosage form. The outputs of the research work divulged that the developed matrix patch of quetiapine for transdermal drug delivery can be a propitious opportunity that affords effective treatment of schizophrenia. Novelty statement The oral route is not suitable for the drugs having extensive first-pass metabolism which leads to reduced bioavailability. For the parenteral route, invasiveness causes the patient noncompliance while sterility contributes to the cost factor. Moreover, the treatment of schizophrenic patients is a challenging task for caregivers and doctors. Hence, the transdermal patch of quetiapine was developed to bypass the biotransformation of drugs and thereby to enhance the bioavailability as well as to provide sustained drug delivery which ultimately reduces the dosage frequency.

Fabrication, optimisation and in vitro evaluation of docetaxel and curcumin Co-loaded nanostructured lipid carriers for improved antitumor activity against non-small cell lung carcinoma.

AIM: To develop docetaxel (DT) and curcumin (CUR) co-loaded nanostructured lipid carriers (DTCR-NLCs) for ratiometric co-targeting to non-small cell lung carcinoma (NSCLC) cells. METHODS: The DTCR-NLCs were developed by employing a high-pressure homogenisation technique and optimised by employing a rotatable central composite design response surface methodology (RCCD-RSM) via the design of experiments (DoE) approach. RESULTS: The optimised DTCR-NLCs had a particle size (D90) of 150.2 ± 5.2 nm, Pdi of 0.263 ± 0.15, zeta potential of +26.3 ± 5.2 mv. The % drug loading (% DL) of DT and CUR was observed to be 1.38 ± 0.98 and 2.99 ± 1.24, respectively. Dissolution studies depicted a pH-independent drug release (≈98% drug release at 144 h). The DTCR-NLCs were stable and haemocompatible. MTT cell viability assay of DTCR-NLCs demonstrated considerably increased cytotoxicity towards NCI-H460 cells. CONCLUSIONS: The developed DTCR-NLCs heralds the future of an efficacious and safer Taxane therapy for NSCLC.

Formulation, optimization, and characterization of rifampicin-loaded solid lipid nanoparticles for the treatment of tuberculosis.

Mycobacterium tuberculosis, being the causative infectious agent, is the leading cause of death worldwide amongst the infectious disease. The low bioavailability of rifampicin (RIF), one of the vital constituent of antitubercular therapy, instigates an urge to develop nanocarrier, which can prevent its degradation in the acidic pH of the stomach. Solid lipid nanoparticles (SLNs) have been proven to be promising versatile platform for oral delivery of lipophilic drugs. Therefore, the current investigation demonstrates development of RIF-loaded solid lipid nanoparticles (RIF-SLNs) using high-pressure homogenization technique by employing a three-level, three-factor Box-Behnken design. Concentration of drug, concentration of emulsifier, and homogenization pressure were selected as an independent variables, and %drug loading (%DL), %entrapment efficiency (%EE), and particle size were selected as dependent variables. The developed RIF-SLNs were characterized for particle size, polydispersity index, zeta potential, %EE, %DL, differential scanning calorimetry, X-ray diffraction, and TEM analysis. The mean diameter of RIF-SLNs was found to be 456 ± 11 nm, %EE of 84.12 ± 2.78%, and %DL of 15.68 ± 1.52%. The in vitro lipolysis experiments revealed that RIF-SLNs stabilized using poloxamer 188, exhibited antilipolytic effect. Furthermore, the in vitro GI stability studies (at pH 1.2, pH 4.5, pH 6.8, and pH 7.4) revealed that the developed system could withstand various gastrointestinal tract media. The in vitro dissolution studies depicted biphasic drug release profile for drug-loaded SLNs revealing best fit with Weibull model. The accelerated stability studies for 6 months does not revealed any significant change in characteristics of developed RIF-SLNs.

Process, optimization, and characterization of budesonide-loaded nanostructured lipid carriers for the treatment of inflammatory bowel disease.

The major challenge involved in the treatment of inflammatory bowel disease is targeted delivery of the drug at the site of inflammation. As nanoparticles possess the ability to accumulate at the site of inflammation, present investigation aims at development of Budesonide-loaded nanostructured lipid carrier systems (BDS-NLCs) for the treatment of inflammatory bowel disease. BDS-NLCs were prepared by employing a high pressure homogenization technique. Various preliminary trials were performed for optimization of the NLCs in which different processes, as well as formulation parameters, were studied. The BDS-NLCs was optimized statistically by applying a 3-factor/3-level Box-Behnken design. Drug concentration, surfactant concentration, and emulsifier concentration were selected as independent variables, and % entrapment efficiency and particle size were selected as dependent variables. The best batch comprises of 10%, 7%, and 20% w/w concentration of drug, surfactant, and emulsifier, respectively, with % entrapment efficiency of 92.66 ± 3.42% and particle size of 284.0 ± 4.53 nm. Further, in order to achieve effective delivery of nanoparticulate system to colonic region, the developed BDS-NLCs were encapsulated in Eudragit® S100-coated pellets. The drug release studies of pellets depict intactness of BDS-NLCs during palletization process, with f2 value of 75.879. The in vitro evaluation of enteric-coated pellets revealed that a coating level of 15% weight gain is needed in order to impart lag time of 5 h (transit time to reach colon). The results of the study demonstrate that the developed BDS-NLCs could be used as a promising tool for the treatment of inflammatory bowel disease.

Development of a novel tablet-in-capsule formulation of mesalamine for inflammatory bowel disease.

OBJECTIVE: The objective of the present work was to develop a tablet-in-capsule type of multiunit system, which releases the drug in a controlled manner at pre-programmed time intervals. METHODS: The system consists of an enteric-coated hydroxypropyl methylcellulose capsule filled with four units of mesalamine minitablets, each of which was further coated with different ratios of Eudragit(®) E100 and Eudragit(®) RS100. RESULTS: In vitro evaluation of tablets coated with Eudragit(®) E100 and Eudragit(®) RS100 at different pH conditions revealed that at lower pH levels (2.0, 3.6 and 5.5 pH), the drug release is mainly governed by the dissolution of Eudragit(®) E100 from the Eudragit(®) E100 and Eudragit(®) RS100 coat. In vitro evaluation of capsules enteric coated with Eudragit(®) L100 and Eudragit(®) S100 revealed that a maximum lag time of 3 h and 4 h was obtained, respectively. In vivo roentgenographic evaluation in rabbits revealed that the developed system remained intact until it reaches the targeted region of the gastrointestinal tract, i.e. ileum and colon, where the tablets were released after the dissolution of the enteric coat Eudragit(®) L100 and Eudragit(®) S100, respectively. CONCLUSION: The developed system exhibited a promising targeting behavior and hence may be used for the treatment of inflammatory bowel disease.

Insights on drug and gene delivery systems in liver fibrosis.

Complications of the liver are amongst the world's worst diseases. Liver fibrosis is the first stage of liver problems, while cirrhosis is the last stage, which can lead to death. The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver's metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting. Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis; nevertheless, the working mechanism of anti-fibrotic medications is not fully understood, and there is a need to design delivery systems that are well-understood and can aid in cirrhosis. Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery. As a result, the capability of nanoparticles in hepatic delivery was explored. Another approach is targeted drug delivery, which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells (HSCs). We have addressed numerous delivery strategies that target HSCs, which can eventually aid in fibrosis. Recently genetics have proved to be useful, and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted. To summarize, this review paper sheds light on the most recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.

Design Considerations, Formulation Approaches, and Strategic Advances of Hydrogel Dressings for Chronic Wound Management.

Wound healing is a complex and dynamic physiological process consisting of a series of cellular and molecular events that initiate immediately after a tissue lesion, to reconstruct the skin layer. It is indubitable that patients with chronic wounds, severely infected wounds, or any metabolic disorder of the wound microenvironment always endure severe pain and discomfort that affect their quality of life. It is essential to treat chronic wounds for conserving the physical as well as mental well-being of affected patients and for convalescing to improve their quality of life. For supporting and augmenting the healing process, the selection of pertinent wound dressing is essential. A substantial reduction in healing duration, disability, associated cost, and risk of recurrent infections can be achieved via engineering wound dressings. Hydrogels play a leading role in the path of engineering ideal wound dressings. Hydrogels, comprising water to a large extent, providing a moist environment, being comfortable to patients, and having biocompatible and biodegradable properties, have found their success as suitable wound dressings in the market. The exploitation of hydrogels is increasing perpetually after substantiation of their broader therapeutic actions owing to their resemblance to dermal tissues, their capability to stimulate partial skin regeneration, and their ability to incorporate therapeutic moieties promoting wound healing. This review entails properties of hydrogel supporting wound healing, types of hydrogels, cross-linking mechanisms, design considerations, and formulation strategies of hydrogel engineering. Various categories of hydrogel wound dressing fabricated recently are discussed based on their gel network composition, degradability, and physical and chemical cross-linking mechanisms, which provide an outlook regarding the importance of tailoring the physicochemical properties of hydrogels. The examples of marketed hydrogel wound dressings are also incorporated along with the future perspectives and challenges associated with them.

Surface-modified nanoparticles of docetaxel for chemotherapy of lung cancer: An intravenous to oral switch.

Despite being potent, the marketed formulations of Docetaxel (DX) are associated with numerous side effects and are meant for intravenous administration. Advanced pharmaceutical nanotechnology has a significant potential to facilitate the 'intravenous (i.v) to oral switch'. The present research work deals with the development of an orally administrable, folate-receptor-targeted Nanostructured lipid carriers (NLCs) of DX (FA-DX-NLCs) for facilitating oral chemotherapy of lung cancer while overcoming the bioavailability and toxicity issues. The nanoformulation prepared to employ high-pressure homogenization and lyophilization, was evaluated and statistically analyzed for various in-vitro and in-vivo formulation characteristics. The lyophilized nanoparticles were observed to be spherical with a particle size of 183.4 ± 2.13 (D90), Pdi of 0.358 ± 0.03, % EE of 82.41 ± 2.44, % DL of 4.41 ± 0.54 and a zeta potential of -3.3 ± 0.7 mv. The increased oral in-vivo bioavailability of DX was evident from the plasma-concentration area under the time curve (AUC0-t), which was âˆ¼ 27-fold greater for FA-DX-NLCs as compared to DX suspension. The orally administered FA-DX-NLCs exhibited excellent antitumor efficacy in a pre-clinical model of lung carcinoma. Tumor staging, histopathology, and immunostaining of the tumors suggested greater anti-proliferative, apoptotic, anti-metastatic, and anti-angiogenic potential as compared to DX-suspension. The pre-clinical toxicity studies affirmed the excellent safety and bio-compatibility of FA-DX-NLCs. The research work presents immense translational potential for switching the DX-based chemotherapy for lung cancer from 'hospital to home.'

New Drug Delivery Systems Developed for Brain Targeting.

The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSF) are two of the most complex and sophisticated concierges that defend the central nervous system (CNS) by numerous mechanisms. While they maintain the neuro-ecological homeostasis through the regulated entry of essential biomolecules, their conservative nature challenges the entry of most of the drugs intended for CNS delivery. Targeted delivery challenges for a diverse spectrum of therapeutic agents/drugs (non-small molecules, small molecules, gene-based therapeutics, protein and peptides, antibodies) are diverse and demand specialized delivery and disease-targeting strategies. This review aims to capture the trends that have shaped the current brain targeting research scenario. This review discusses the physiological, neuropharmacological, and etiological factors that participate in the transportation of various drug delivery cargoes across the BBB/BCSF and influence their therapeutic intracranial concentrations. Recent research works spanning various invasive, minimally invasive, and non-invasive brain- targeting approaches are discussed. While the pre-clinical outcomes from many of these approaches seem promising, further research is warranted to overcome the translational glitches that prevent their clinical use. Non-invasive approaches like intranasal administration, P-glycoprotein (P-gp) inhibition, pro-drugs, and carrier/targeted nanocarrier-aided delivery systems (alone or often in combination) hold positive clinical prospects for brain targeting if explored further in the right direction.

Triumph against cancer: invading colorectal cancer with nanotechnology.

INTRODUCTION: Recent statistics have reported colorectal cancer (CRC) as the second leading cause of cancer-associated deaths in the world. Early diagnosis of CRC may help to reduce the mortality and associated complications. However, the conventional diagnostic techniques often lead to misdiagnosis, fail to differentiate benign from malignant tissue or diagnose only at an advanced stage. For the treatment of CRC, surgery, chemotherapy, immunotherapy, and radiotherapy have been employed. However, the quality of living of the CRC patients is highly compromised after employing current therapeutic approaches owing to the toxicity issues and relapse. AREA COVERED: This review accentuates the molecular mechanisms involved in the pathogenesis, stages of CRC, conventional approaches for diagnosis and therapy of CRC and the issues confronted thereby. It provides an outlook on the advantages of employing nanotechnology-based approaches for prevention, early diagnosis, and treatment of CRC. EXPERT OPINION: Employing nanotechnology-based approaches has demonstrated promising outcomes in the prevention, diagnosis, and treatment of CRC. Nanotechnology-based approaches can surmount the major drawbacks of traditional diagnostic and therapeutic approaches. Nanotechnology bestows the advantage of early detection of CRC which helps to undertake instant steps for offering efficient therapy and reducing the mortality rates. For the treatment of CRC, nanocarriers offer the benefit of achieving controlled drug release, improved drug bioavailability, enhanced tumor targetability and reduced adverse effects.

Fabrication and Characterization of Surface Engineered Rifampicin Loaded Lipid Nanoparticulate Systems for the Potential Treatment of Tuberculosis: An In Vitro and In Vivo Evaluation.

The main aim of the present investigation highlights the development of mannose appended rifampicin containing solid lipid nanoparticles (Mn-RIF-SLNs) for the management of pulmonary TB. The developed Mn-RIF-SLNs showed particle size of Mn-RIF-SLNs (479 ± 13 nm) which was found to be greater than that of unconjugated SLNs (456 ± 11 nm), with marginal reduction in percentage entrapment efficiency (79.41 ± 2.42%). The in vitro dissolution studies depicted an initial burst release followed by sustained release profile indicating biphasic release pattern, close-fitting Weibull model having least F-value. The cytotoxicity studies using J774A.1 cell line represented that the developed SLNs were non-toxic and safe as compared to free drug. Fluorescence imaging and flow cytometric (FACS) analysis depicted significant (1.79-folds) intracellular uptake of coumarin-6 (fluorescent marker) loaded Mn-C6-SLNs. The in vivo pharmacokinetic studies in sprague-dawley rats were performed and Mn-RIF-SLNs showed remarkable enhancement in terms of relative bioavailability (~17-folds) as compared to its drug solution via oral administration. The biodistribution studies revealed higher lung accumulation (1.8-folds) of Mn-RIF-SLNs as compared to the Un-RIF-SLNs. In conclusion, the developed Mn-RIF-SLNs could serve as a promising tool for delivering the drug cargo to the site of infection (lungs) in the treatment of TB.

Fabrication and in vivo evaluation of ligand appended paclitaxel and artemether loaded lipid nanoparticulate systems for the treatment of NSCLC: A nanoparticle assisted combination oncotherapy.

The aim of present study was to develop folate appended PEGylated solid lipid nanoparticles(SLNs) of paclitaxel(FPS) and artemether(FAS). The SLNs were prepared by employing high pressure homogenization technique. The results of MTT assays revealed better cytotoxicity of FPS when given in combination with FAS on human lung cancer cell line H-1299 as compared to pure drugs, unconjugated SLNs and FPS alone. The cellular uptake of FPS and FAS was confirmed by fluorescence imaging and flow cytometric analysis. In-vivo pharmacokinetic study revealed better absorption and long circulation of FPS and FAS, which further leads to increased relative bioavailability of drugs(13.81-folds and 7.07-folds for PTX and ART, respectively) as compared to their solutions counterpart. In-vivo pharmacodynamic study confirmed tumor regression of developed SLNs formulations, which was observed highest when used in combination of FPS and FAS. Serum creatinine, blood urea nitrogen(BUN), SGOT, albumin and total protein levels revealed that formulated FPS and FAS does not exhibit any renal and hepatic toxicity. It can be concluded that by administering ART-SLNs along with PTX-SLNs via oral route, anticancer potential of PTX was improved without any toxicity (both renal, hepatic), thus, indicating the potential of developed formulations in reducing dose related toxicity of PTX.

Getting into the brain: approaches to enhance brain drug delivery.

Being the most delicate organ of the body, the brain is protected against potentially toxic substances by the blood-brain barrier (BBB), which restricts the entry of most pharmaceuticals into the brain. The developmental process for new drugs for the treatment of CNS disorders has not kept pace with progress in molecular neurosciences because most of the new drugs discovered are unable to cross the BBB. The clinical failure of CNS drug delivery may be attributed largely to a lack of appropriate drug delivery systems. Localized and controlled delivery of drugs at their desired site of action is preferred because it reduces toxicity and increases treatment efficiency. The present review provides an insight into some of the recent advances made in the field of brain drug delivery.The various strategies that have been explored to increase drug delivery into the brain include (i) chemical delivery systems, such as lipid-mediated transport, the prodrug approach and the lock-in system; (ii) biological delivery systems, in which pharmaceuticals are re-engineered to cross the BBB via specific endogenous transporters localized within the brain capillary endothelium; (iii) disruption of the BBB, for example by modification of tight junctions, which causes a controlled and transient increase in the permeability of brain capillaries; (iv) the use of molecular Trojan horses, such as peptidomimetic monoclonal antibodies to transport large molecules (e.g. antibodies, recombinant proteins, nonviral gene medicines or RNA interference drugs) across the BBB; and (v) particulate drug carrier systems. Receptor-mediated transport systems exist for certain endogenous peptides, such as insulin and transferrin, enabling these molecules to cross the BBB in vivo.The use of polymers for local drug delivery has greatly expanded the spectrum of drugs available for the treatment of brain diseases, such as malignant tumours and Alzheimer's disease. In addition, various drug delivery systems (e.g. liposomes, microspheres, nanoparticles, nanogels and bionanocapsules) have been used to enhance drug delivery to the brain. Recently, microchips and biodegradable polymers have become important in brain tumour therapy.The intense search for alternative routes of drug delivery (e.g. intranasal drug delivery, convection-enhanced diffusion and intrathecal/intraventricular drug delivery systems) has been driven by the need to overcome the physiological barriers of the brain and to achieve high drug concentrations within the brain. For more than 30 years, considerable efforts have been made to enhance the delivery of therapeutic molecules across the vascular barriers of the CNS. The current challenge is to develop drug delivery strategies that will allow the passage of drug molecules through the BBB in a safe and effective manner.

Design, development and optimization of a novel time and pH-dependent colon targeted drug delivery system.

The aim of present study was to develop a time- and pH-dependent system for delivering mesalamine to the colon. The system consists of the core tablet of mesalamine which is compression coated with hydroxypropyl methylcellulose (HPMC K4M) (time-dependent factor). This is then coated with pH-dependent polymer Eudragit L100. The simplex lattice design was adopted to optimize the independent variables i.e. amount of HPMC (X1), dextrose (X2) and polyvinyl pyrollidone (PVP) (X3) and to study their effect on the dependent variables i.e. lag time and time for 50% drug dissolution (t50). The results of the linear interactive model and graphical representation revealed that as the amount of HPMC increases, the lag time and t50 value also increases and as the amount of dextrose and PVP were increased the lag time and t50 value decreases.

Threatening cancer with nanoparticle aided combination oncotherapy.

Employing combination therapy has become obligatory in cancer cases exhibiting high tumor load, chemoresistant tumor population, and advanced disease stages. Realization of this fact has now led many of the combination oncotherapies to become an integral part of anticancer regimens. Combination oncotherapy may encompass a combination of anticancer agents belonging to a similar therapeutic category or that of different therapeutic categories (e.g. chemotherapy + gene therapy). Differences in the physicochemical properties, pharmacokinetics and biodistribution pattern of different payloads are the major constraints that are faced by combination chemotherapy. Concordant efforts in the field of nanotechnology and oncology have emerged with several approaches to solve the major issues encountered by combination therapy. Unique colloidal behaviors of various types of nanoparticles and differential targeting strategies have accorded an unprecedented ability to optimize combination oncotherapeutic delivery. Nanocarrier based delivery of the various types of payloads such as chemotherapeutic agents and other anticancer therapeutics such as small interfering ribonucleic acid (siRNA), chemosensitizers, radiosensitizers, and antiangiogenic agents have been addressed in the present review. Various nano-delivery systems like liposomes, polymeric nanoparticles, polymerosomes, dendrimers, micelles, lipid based nanoparticles, prodrug based nanocarriers, polymer-drug conjugates, polymer-lipid hybrid nanoparticles, carbon nanotubes, nanosponges, supramolecular nanocarriers and inorganic nanoparticles (gold nanoparticles, silver nanoparticles, magnetic nanoparticles and mesoporous silica based nanoparticles) that have been extensively explored for the formulation of multidrug delivery is an imperative part of discussion in the review. The present review features the outweighing benefits of combination therapy over mono-oncotherapy and discusses several existent nanoformulation strategies that facilitate a successful combination oncotherapy. Several obstacles that may impede in transforming nanotechnology-based combination oncotherapy from bench to bedside, and challenges associated therein have also been discussed in the present review.

Oral Delivery of Anticancer Agents Using Nanoparticulate Drug Delivery System.

BACKGROUND: Conventionally, anti-cancer agents were administered through the intravenous route. The major drawbacks associated with the intravenous route of administration are: severe side effects, need of hospitalization, nursing care, and palliative treatment. In order to overcome the drawbacks associated with the intravenous route of administration, oral delivery of anti-cancer agents has gained tremendous interest among the scientific fraternity. Oral delivery of anti-cancer agents principally leads to a reduction in the overall cost of treatment, and aids in improving the quality of life of patients. Bioavailability of drugs and inter-subject variability are the major concerns with oral administration of anti-cancer agents. Factors viz. physicochemical and biological barriers (pre-systemic metabolism and transmembrane efflux of the drug) are accountable for hampering oral bioavailability of anti-cancer agents can be efficiently overcome by employing nanocarrier based drug delivery systems. Oral delivery of anticancer agents by employing these drug delivery systems will not only improve the quality of life of patients but will also provide pharmacoeconomic advantage and lead to a reduction in the overall cost of treatment of life-threatening disease like cancer. OBJECTIVE: This article aims to familiarize the readers with some of the recent advancements in the field of nanobased drug delivery systems for oral delivery of anticancer agents. CONCLUSION: Advancement in the field of nanotechnology-based drug delivery systems has opened up gateways for the delivery of drugs that are difficult to administer orally. Oral delivery of anti-cancer agents by these drug delivery systems will not only improve the quality of life of patients but will also provide pharmacoeconomic advantage and lead to a reduction in the overall cost of treatment of life-threatening disease like cancer.

Long-Acting Injectables: Current Perspectives and Future Promise.

The parenteral route of administration is preferred over the oral route for treatment of many chronic and life-threatening diseases due to better patient compliance. Long-acting injectables/depot delivery systems are formulations intended for prolonged/sustained drug release over a long period of time ranging from a few days to months. Depot delivery systems enhance product quality by decreasing dosing frequency, simplifying the drug regimen. Parenteral depots reduce the relapse rate of disease and the maintenance phase of therapy, hence improving efficacy and treatment adherence. However, despite being extensively explored in the last seventy years, only a few depot products have been marketed or have reached commercial viability. The introduction of long-acting injectables of any drug took 9 to 10 years after approval of its oral formulation. Mainly the market has been conquered by long-acting injectables for antipsychotic, substance abuse, and hormonal therapy drugs. This article focuses on the preparation of long-acting injectables with special emphasis on challenges associated with formulation. The evolution and current global market trend of various depot formulations are also discussed. Insight is provided into the promising future of long-acting injectables of protein-based drugs as well as multidrug therapy, along with potential uses in the treatment of chronic diseases like HIV, Parkinson's, and Alzheimer's.

Repurposing of sodium valproate in colon cancer associated with diabetes mellitus: Role of HDAC inhibition.

BACKGROUND AND PURPOSE: Diabetic patients are at greater risk for colon cancer. Histone deacetylases (HDACs) serve as common target for both. The key objective of the study was to evaluate the effect of sodium valproate in type 2 diabetes mellitus associated colon cancer. EXPERIMENTAL APPROACH: High fat diet and streptozotocin were used to induce type 2 diabetes. Following this, after diabetes confirmation, colon cancer was induced using 1,2 dimethylhydrazine (25 mg/kg, s.c.) once weekly from 7th week to 20th weeks. Sodium valproate (200 mg/kg) treatment was given from 20th to 24th week. At the end of 24 weeks, several enzymatic and biochemical parameters, were estimated. MTT, clonogenic and scratch wound healing assay were carried out in HCT-15 cell line. KEY RESULTS: Hyperglycemia, hyperinsulinemia, increase in cytokines (TNF-α and IL-1ß) and carcinoembryonic antigen and presence of proliferating cells was seen in disease control animals which was prevented by sodium valproate treatment. Overexpression of relative HDAC2 mRNA levels was found in diseased control animals, which was reduced by sodium valproate treatment. IC50 of sodium valproate was found to be 3.40 mM and 3.73 mM at 48 h and 72 h respectively on HCT-15 cell line. Sodium valproate also dose dependently prevented colony formation and cell migration. CONCLUSION AND IMPLICATIONS: Sodium valproate can be considered for repurposing in colon cancer associated with diabetes mellitus.